The idea of using proteases in treating cancer has been around for more than a 100 years. In 1905, John Beard proposed the use of fresh pancreatic enzyme extracts as a possible cancer therapy and conducted successful experiments with Jersen's mouse sarcoma model. After injecting the mouse with the protease enzyme trypsin, a regression of tumours was observed. The results obtained by Beard produced great interest at that time, and crude enzyme extracts prepared from sheep pancreas were used to treat human cancer patients to reduce tumour progression and prolong survival time.
More recently, oral administration of enzymes has been shown to be well tolerated by patients with good survival rates across a range of cancers including pancreatic, bowel, colorectal and late stage myelomas. The use of high dosages of enzymes has been required because of loss and inactivation through digestion and from other enzyme inactivators in blood plasma such as serpins.
The use of proenzymes (inactive precursor form of enzymes) has been used to overcome problems encountered with the oral administration of enzymes. A proenzyme mixture including trypsinogen, which is the proenzyme form of the serine protease inhibitor trypsin, has been shown to be useful in treating carcinomas and believed to be selectively activated at the surface of tumour cells (Novak J and Trnka F, Proenzyme Therapy of Cancer, Anticancer Research, 25: 1157-1178, 2005; U.S. Pat. No. 5,858,357). The mechanism of action of trypsin is believed to occur by way of proteolysis of the tumour cells.
A need exists to identify and provide enhanced proenzyme compositions that are effective for treating cancers.